Neurons contact each other mostly by synaptic transmission at synapses. The maintenance of synaptic transmission relies on vesicle endocytosis, which recycles fused vesicles for the second round of exocytosis. My goal is to improve our understanding on the cellular and molecular mechanisms underlying synaptic vesicle endocytosis, which are the building block for the maintenance of synaptic transmission and thus the signaling process of the nervous system. First, we found that two mostly widely observed forms of endocytosis, the rapid clathrin-independent, and the slow clathrin-dependent endocytosis is initiated by calcium/calmodulin-activated calcineurin, which dephosphorylates many endocytic proteins (Sun et al., J Neurosci, 2010). Second, auxilin is generally thought to be involved in clathrin-dependent endocytosis by decoating of clathrin. We found surprisingly that auxilin is involved in controlling the rate of endocytosis, which is critical for the maintenance of synaptic transmission during repetitive firing in physiological conditions (Yim et al., 2010). Third, although endocytosis is crucial for recycling and maintaining synaptic transmission, how it is initiated and controlled is not well understood.